Diabetes is a major public health epidemic in the United States. The aetiology of diabetes is hyperglycemia, which have a tremendous impact on morbidity when left untreated. Diabetes is associated with an increased risk for a number of complications including, heart disease and stroke, high blood pressure, blindness, kidney disease, nervous system disease, amputation, dental disease, and pregnancy complications.
Diabetes is classified into two types: Type 1 and Type 2. Type 1 diabetes, also known as insulin-dependent diabetes mellitus (IDDM), is believed to be caused by autoimmune destruction of pancreatic beta cells, which produce and secrete insulin. Type 2 diabetes, also known as non-insulin-dependent diabetes mellitus (NIDDM), is characterized by the failure of the body to respond normally to insulin and a gradual loss in the ability of the pancreas to produce insulin.
Insulin-like growth factor binding protein-2 (“IGFBP-2”) is one of 6 homologous IGFBPs and the second most abundant IGFBP in serum (Jones, J. I. & Clemmons, D. R. Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev. 16, 3-34 (1995)). IGFBPs are thought to inhibit the action of insulin-like growth factors (“IGFs”) through high-affinity binding that regulates access of IFGs to target tissues and reduce IGF bioactivity. IGFBP-2 has been linked with Type 2 diabetes in several large genome wide association studies (Grarup et al. 56 Diabetes 3105-3111 (2007)). Transgenic IGFBP-2 over-expression in mice showed reduced diet-induced obesity and associated complications (Wheatcroft et al., 56 Diabetes 285-294 (2007)). A direct role for IGFBP-2 in glucose metabolism and insulin regulation however, has not been established.
Currently therapies for diabetes tend to focus on insulin-replacement or augmentation. Accordingly, a need exists for additional treatment options.